Synthesis, structural aspects and electrochemistry of ferrocene-containing betadiketonato titanium(IV) complexes with biomedical applications
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Date
2006-05
Authors
Barnard, Nicola Isabel
Journal Title
Journal ISSN
Volume Title
Publisher
University of the Free State
Abstract
English: In this study ferrocene-containing β-diketones of the type [FcCOCH2COR] where R = Ph, CH3, CF3,
Fc and Rc (Fc = ferrocenyl and Rc = ruthenocenyl) and β-diketonato titanium(IV) complexes of the
type [Cp2Ti(FcCOCHCOR)]+ClO4
-, [(β-diketonato)2TiCl2] and [(β-diketonato)2Ti(Fc-CH(CH3)O)2]
were synthesised. Eleven of these compounds were previously unknown.
Complexes were characterised by 1H NMR spectroscopy and the structures of [RcCOCH2COFc] and
[Cp2Ti(FcCOCHCOCH3)]+ClO4
-, as representative examples of two of the synthesised classes of
complexes, were determined using single crystal crystallographic techniques.
Electrochemical studies were conducted in dichloromethane in the presence of [NBu4][B(C6F5)4] as
uncoordinating supporting electrolyte. Dimerization of the ruthenocenium fragment of the β-diketone
[RcCOCH2COFc] was not as prominent as that of free ruthenocene. The Ru3+/Ru2+ couple displayed
irreversible electrochemistry while the Fc/Fc+ couple was electrochemically reversible. For the Ti
complexes, electrochemically quazi-reversible to irreversible behaviour was observed for the Ti4+/Ti3+
couple, while the Fc/Fc+ couples were mostly found to be electrochemically quasi-reversible and
chemically reversible. In addition, for the mono-β-diketonato titanium(IV) salts, a splitting of the
ferrocenyl peaks was discernable. This phenomenon is exceptional. A unique monomer/dimer
equilibrium was proposed as a possible explanation for this observation. Intra-molecular
communication between the iron centres of [(FcCOCHCOPh)2Ti(Fc-CH(CH3)O)2] allowed
electrochemical detection of all four ferrocenyl centres.
Cytotoxic studies revealed that complexes [Cp2Ti(FcCOCHCOR)]+ClO4
-, which contain the titanium
and ferrocenyl antineoplastic moieties, were more effective in killing CoLo and HeLa cancer cell lines
than the parent titanocene dichloride compound which is currently in phase II clinical trials. These
results are attributed to a synergistic effect between different fragments possessing anti-cancer activity
in the same molecule.
Afrikaans: In hierdie studie is ferroseen-bevattende β-diketone van [FcCOCH2COR] vorm met R = Ph, CH3, CF3, Fc en Rc (Fc = ferroseniel en Rc = rutenoseniel) as ook β-diketonato titanium(IV) komplekse van vorm [Cp2Ti(FcCOCHCOR)]+ClO4 -, [(β-diketonato)2TiCl2] en [(β-diketonato)2Ti(Fc-CH(CH3)O)2] gesintetiseer. Elf van hierdie verbindings was tot nou toe onbekend. Die komplekse was gekarakteriseer met behulp van 1H KMR spektroskopie. Die strukture van [RcCOCH2COFc] en [Cp2Ti(FcCOCHCOCH3)]+ClO4 -, as verteenwoordigend van twee van die gesintetiseerde kompleksklasse was ook deur enkelkristal kristalografiese tegnieke bepaal. Elektrochemiese studies was uitgevoer in diclorometaan in die teenwoordigheid van [NBu4][B(C6F5)4] as nie-koördinerende ondersteuningselektroliet. Dimerisasie van die rutenosenium fragment van die [RcCOCH2COFc] β-diketoon was minder prominent as vir vry rutenoseen. Onomkeerbare elektrochemie was vir die Ru2+/Ru3+ koppel waargeneem terwyl elektrochemiese omkeerbaarheid vir die Fc/Fc+ koppel waargeneem was. Vir die Ti komplekse was elektrochemiese kwasiomkeerbaarheid tot onomkeerbaarheid is vir die Ti4+/Ti3+ koppel gevind, terwyl die Fc/Fc+ koppels elektrochemiese kwasi-omkeerbaarheid en chemiese omkeerbare gedrag getoon het. Die Fc/Fc+ koppels het ook splyting in die mono-β-diketonato titanium(IV) soute getoon. Die verskynsel is buite gewoon. ‘n Unieke monomeer/dimeer ewewig is as ‘n moontlike verduideliking vir hierdie waarneming voorgehou. Intra-molekulêre komunikasie tussen die ysterkerne van [(FcCOCHCOPh)2Ti(Fc-CH(CH3)O)2] het elektrochemiese waarneming van al vier ferroseniel groepe toegelaat. Sitotoksiese studies het getoon dat die antineoplastiese titanium- en ferrosenielbevattende [Cp2Ti(RcCOCHCOR)]+ClO4 - komplekse, meer effektief CoLo en HeLa kankersellyne vernietig as titanoseendicloried wat huidiglik in fase II kliniese proewe is. Hierdie resultaat is toegeskryf aan ‘n sinergistiese effek wat tussen die verskillende kankerbestrydende molekulêre fragmente bestaan.
Afrikaans: In hierdie studie is ferroseen-bevattende β-diketone van [FcCOCH2COR] vorm met R = Ph, CH3, CF3, Fc en Rc (Fc = ferroseniel en Rc = rutenoseniel) as ook β-diketonato titanium(IV) komplekse van vorm [Cp2Ti(FcCOCHCOR)]+ClO4 -, [(β-diketonato)2TiCl2] en [(β-diketonato)2Ti(Fc-CH(CH3)O)2] gesintetiseer. Elf van hierdie verbindings was tot nou toe onbekend. Die komplekse was gekarakteriseer met behulp van 1H KMR spektroskopie. Die strukture van [RcCOCH2COFc] en [Cp2Ti(FcCOCHCOCH3)]+ClO4 -, as verteenwoordigend van twee van die gesintetiseerde kompleksklasse was ook deur enkelkristal kristalografiese tegnieke bepaal. Elektrochemiese studies was uitgevoer in diclorometaan in die teenwoordigheid van [NBu4][B(C6F5)4] as nie-koördinerende ondersteuningselektroliet. Dimerisasie van die rutenosenium fragment van die [RcCOCH2COFc] β-diketoon was minder prominent as vir vry rutenoseen. Onomkeerbare elektrochemie was vir die Ru2+/Ru3+ koppel waargeneem terwyl elektrochemiese omkeerbaarheid vir die Fc/Fc+ koppel waargeneem was. Vir die Ti komplekse was elektrochemiese kwasiomkeerbaarheid tot onomkeerbaarheid is vir die Ti4+/Ti3+ koppel gevind, terwyl die Fc/Fc+ koppels elektrochemiese kwasi-omkeerbaarheid en chemiese omkeerbare gedrag getoon het. Die Fc/Fc+ koppels het ook splyting in die mono-β-diketonato titanium(IV) soute getoon. Die verskynsel is buite gewoon. ‘n Unieke monomeer/dimeer ewewig is as ‘n moontlike verduideliking vir hierdie waarneming voorgehou. Intra-molekulêre komunikasie tussen die ysterkerne van [(FcCOCHCOPh)2Ti(Fc-CH(CH3)O)2] het elektrochemiese waarneming van al vier ferroseniel groepe toegelaat. Sitotoksiese studies het getoon dat die antineoplastiese titanium- en ferrosenielbevattende [Cp2Ti(RcCOCHCOR)]+ClO4 - komplekse, meer effektief CoLo en HeLa kankersellyne vernietig as titanoseendicloried wat huidiglik in fase II kliniese proewe is. Hierdie resultaat is toegeskryf aan ‘n sinergistiese effek wat tussen die verskillende kankerbestrydende molekulêre fragmente bestaan.
Description
Keywords
Titanium, Ferrocene, Ruthenocene, β-diketones, Electrochemistry, Cytotoxicity, Metallocenes, Organometallic compounds, Titanium -- Synthesis, Dissertation (M.Sc. (Chemistry))--University of the Free State, 2006